Zilpaterol is a known adrenergic β-2 agonist corresponding in structure to Formula (I):
The IUPAC name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-(isopropylamino) imidazo[4,5,1-jk]-[1]benzazepin-2(1H)-one. The Chemical Abstracts name for zilpaterol is 4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methyl-ethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one.
Zilpaterol hydrochloride is sold by Merck Animal Health, under the trademark ZILMAX®. It is approved in the United States for increased rate of weight gain, improved feed efficiency, and increased carcass leanness in cattle fed in confinement for slaughter during the last 20 to 40 days on feed. The approved inclusion rate of zilpaterol hydrochloride is 6.8 grams/ton (7.5 ppm) in feed (see Freedom of Information Summary for NADA 141-258, approved Aug. 10, 2006).
In U.S. Pat. No. 4,585,770, Fréchet et al. discuss compounds, such as zilpaterol, encompassed by a genus characterized as 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-j-k][1]-benzazepin-2-(1H)-one derivatives and acid addition salts thereof.
In U.S. Pat. No. 4,900,735, Grandadam discusses a zootechnical composition comprising zilpaterol and acid addition salts thereof. Grandadam states that such a composition may be used in general to increase the weight of cattle, pigs, sheep, and poultry.
In U.S. Pat. Nos. 5,731,028 and 5,847,124, Chevremont et al. discuss crystallized anhydrous zilpaterol hydrochloride, and particularly crystallized anhydrous zilpaterol hydrochloride wherein less than 5% of the crystals have a size of less than 15 μm, and at least 95% of the crystals have a size of less than 250 μm. According to Chevremont et al., such crystals may be incorporated into animal feed to increase body weight and meat quality. Chevremont et al. provide methods for making such crystals, and discuss using the crystals to make animal premixes in which the crystals are secured to a corn cob support having a greater particle size.
WO2013/171330 discloses a method of enhancing the performance of broiler chickens using zilpaterol containing feed.
WO2014/140237 discloses a method of improving the efficiency of beef production from bovine animals which comprises feeding zilpaterol to the animals.
EP0197188 describes a method of preparing non dusty blend of meals or flours with additives for use in fodder manufacturing and or for livestock feeding. Specifically, the method involves the blending of the meal or flour with a nonionic physiologically compatible surfactant such as esters of propylene glycol. The active ingredient exemplified is Carbadox. Zilpaterol is not disclosed.
Ractopamine hydrochloride is sold by Elanco Animal Health under the trademark Optaflexx®. It is approved in the United States for increasing the rate of weight gain, improving feed efficiency in cattle fed in confinement for slaughter during the last 28 to 42 days on feed. The approved inclusion rate of ractopamine hydrochloride is 10 to 30 ppm (see Freedom of Information Summary for NADA 141-221, approved Jun. 13, 2003).